SETD1A p.Ser1550=
c.4650C>T · VCV4929526
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0512%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -4.6 |
| Overall | ||
| CADD | 0.596 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0512%
European (non-Finnish) · 604/1,179,902 alleles
Filtering AF
0.0478%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0465%
Overall
0.0389%
628/1,613,046 alleles · ultra-rare
exomes 590/1,460,994 · genomes 38/152,052 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0512% | 1,953 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,464 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.01% | 9,997 |
| Finnishnot grpmax-eligible | 0.00158% | 63,254 |
| African / African-American | 0.00133% | 74,952 |
| South Asian | 0.0011% | 91,062 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SETD1A
- Protein
- p.Ser1550=
- Coding
- c.4650C>T
- MANE Select
- NM_014712
- Type
- single nucleotide variant
- Location
- chr16:30980807 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 1550
- a UniProt-annotated variant site (in nedsid)
Similar variants
- SETD1A c.518-2A>G Pathogenic ★★ same type
- SETD1A p.Arg1571Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Arg176Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Arg668Ter Pathogenic ★★ same type
- SETD1A p.Arg913Cys Likely pathogenic ★★ ⚠ same type
- SETD1A p.Arg990Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Tyr646Ter Pathogenic ★★ same type
- SETD1A c.4692+3G>A Uncertain significance ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/setd1a-p-ser1550 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown